The Management of Myelomeningocele Study: obstetrical outcomes and risk factors for obstetrical complications following prenatal surgery.

BACKGROUND: The Management of Myelomeningocele Study was a multicenter randomized trial to compare prenatal and standard postnatal closure of myelomeningocele. The trial was stopped early at recommendation of the data and safety monitoring committee and outcome data for 158 of the 183 randomized women published. OBJECTIVE: In this report, pregnancy outcomes for the complete trial cohort are presented. We also sought to analyze risk factors for adverse pregnancy outcome among those women who underwent prenatal myelomeningocele repair. STUDY DESIGN: Pregnancy outcomes were compared between the 2 surgery groups. For women who underwent prenatal surgery, antecedent demographic, surgical, and pregnancy complication risk factors were evaluated for the following outcomes: premature spontaneous membrane rupture ≤34 weeks 0 days (preterm premature rupture of membranes), spontaneous membrane rupture at any gestational age, preterm delivery at ≤34 weeks 0 days, nonintact hysterotomy (minimal uterine wall tissue between fetal membranes and uterine serosa, or partial or complete dehiscence at delivery), and chorioamniotic membrane separation. Risk factors were evaluated using χ2 and Wilcoxon tests and multivariable logistic regression. RESULTS: A total of 183 women were randomized: 91 to prenatal and 92 to postnatal surgery groups. Analysis of the complete cohort confirmed initial findings: that prenatal surgery was associated with an increased risk for membrane separation, oligohydramnios, spontaneous membrane rupture, spontaneous onset of labor, and earlier gestational age at birth. In multivariable logistic regression of the prenatal surgery group adjusting for clinical center, earlier gestational age at surgery and chorioamniotic membrane separation were associated with increased risk of spontaneous membrane rupture (odds ratio, 1.49; 95% confidence interval, 1.01-2.22; and odds ratio, 2.96, 95% confidence interval, 1.05-8.35, respectively). Oligohydramnios was associated with an increased risk of subsequent preterm delivery (odds ratio, 9.21; 95% confidence interval, 2.19-38.78). Nulliparity was a risk factor for nonintact hysterotomy (odds ratio, 3.68; 95% confidence interval, 1.35-10.05). CONCLUSION: Despite the confirmed benefits of prenatal surgery, considerable maternal and fetal risk exists compared with postnatal repair. Early gestational age at surgery and development of chorioamniotic membrane separation are risk factors for ruptured membranes. Oligohydramnios is a risk factor for preterm delivery and nulliparity is a risk factor for nonintact hysterotomy at delivery.

Bladder Function After Fetal Surgery for Myelomeningocele.

BACKGROUND: A substudy of the Management of Myelomeningocele Study evaluating urological outcomes was conducted. METHODS: Pregnant women diagnosed with fetal myelomeningocele were randomly assigned to either prenatal or standard postnatal surgical repair. The substudy included patients randomly assigned after April 18, 2005. The primary outcome was defined in their children as death or the need for clean intermittent catheterization (CIC) by 30 months of age characterized by prespecified criteria. Secondary outcomes included bladder and kidney abnormalities observed by urodynamics and renal/bladder ultrasound at 12 and 30 months, which were analyzed as repeated measures. RESULTS: Of the 115 women enrolled in the substudy, the primary outcome occurred in 52% of children in the prenatal surgery group and 66% in the postnatal surgery group (relative risk [RR]: 0.78; 95% confidence interval [CI]: 0.57-1.07). Actual rates of CIC use were 38% and 51% in the prenatal and postnatal surgery groups, respectively (RR: 0.74; 95% CI: 0.48-1.12). Prenatal surgery resulted in less trabeculation (RR: 0.39; 95% CI: 0.19-0.79) and fewer cases of open bladder neck on urodynamics (RR: 0.61; 95% CI: 0.40-0.92) after adjustment by child's gender and lesion level. The difference in trabeculation was confirmed by ultrasound. CONCLUSIONS: Prenatal surgery did not significantly reduce the need for CIC by 30 months of age but was associated with less bladder trabeculation and open bladder neck. The implications of these findings are unclear now, but support the need for long-term urologic follow-up of patients with myelomeningocele regardless of type of surgical repair.

Reducing perinatal complications and preterm delivery for patients undergoing in utero closure of fetal myelomeningocele: further modifications to the multidisciplinary surgical technique.

UNLABELLED: OBJECT.: As more pediatric neurosurgeons become involved with fetal myelomeningocele closure efforts, examining refined techniques in the overall surgical approach that could maximize beneficial outcomes becomes critical. The authors compared outcomes for patients who had undergone a modified technique with those for patients who had undergone fetal repair as part of the earlier Management of Myelomeningocele Study (MOMS). METHODS: Demographic and outcomes data were collected for a series of 43 delivered patients who had undergone in utero myelomeningocele closure at the Fetal Center at Vanderbilt from March 2011 through January 2013 (the study cohort) and were compared with data for 78 patients who had undergone fetal repair as part of MOMS (the MOMS cohort). For the study cohort, no uterine trocar was used, and uterine entry, manipulation, and closure were modified to minimize separation of the amniotic membrane. Weekly ultrasound reports were obtained from primary maternal-fetal medicine providers and reviewed. A test for normality revealed that distribution for the study cohort was normal; therefore, parametric statistics were used for comparisons. RESULTS: The incidence of premature rupture of membranes (22% vs 46%, p = 0.011) and chorioamnion separation (0% vs 26%, p < 0.001) were lower for the study cohort than for the MOMS cohort. Incidence of oligohydramnios did not differ between the cohorts. The mean (± SD) gestational age of 34.4 (± 6.6) weeks for the study cohort was similar to that for the MOMS cohort (34.1 ± 3.1 weeks). However, the proportion of infants born at term (37 weeks or greater) was significantly higher for the study cohort (16 of 41; 39%) than for the MOMS cohort (16 of 78; 21%) (p = 0.030). Compared with 10 (13%) of 78 patients in the MOMS cohort, only 2 (4%) of 41 infants in the study cohort were delivered earlier than 30 weeks of gestation (p = 0.084, approaching significance). For the study cohort, 2 fetal deaths were attributed to the intervention, and both were believed to be associated with placental disruption; one of these mothers had previously unidentified thrombophilia. Mortality rates did not statistically differ between the cohorts. CONCLUSIONS: These early results suggest that careful attention to uterine entry, manipulation, and closure by the surgical team can result in a decreased rate of premature rupture of membranes and chorioamnion separation and can reduce early preterm delivery. Although these results are promising, their confirmation will require further study of a larger series of patients.

A randomized trial of prenatal versus postnatal repair of myelomeningocele.

BACKGROUND: Prenatal repair of myelomeningocele, the most common form of spina bifida, may result in better neurologic function than repair deferred until after delivery. We compared outcomes of in utero repair with standard postnatal repair. METHODS: We randomly assigned eligible women to undergo either prenatal surgery before 26 weeks of gestation or standard postnatal repair. One primary outcome was a composite of fetal or neonatal death or the need for placement of a cerebrospinal fluid shunt by the age of 12 months. Another primary outcome at 30 months was a composite of mental development and motor function. RESULTS: The trial was stopped for efficacy of prenatal surgery after the recruitment of 183 of a planned 200 patients. This report is based on results in 158 patients whose children were evaluated at 12 months. The first primary outcome occurred in 68% of the infants in the prenatal-surgery group and in 98% of those in the postnatal-surgery group (relative risk, 0.70; 97.7% confidence interval [CI], 0.58 to 0.84; P<0.001). Actual rates of shunt placement were 40% in the prenatal-surgery group and 82% in the postnatal-surgery group (relative risk, 0.48; 97.7% CI, 0.36 to 0.64; P<0.001). Prenatal surgery also resulted in improvement in the composite score for mental development and motor function at 30 months (P=0.007) and in improvement in several secondary outcomes, including hindbrain herniation by 12 months and ambulation by 30 months. However, prenatal surgery was associated with an increased risk of preterm delivery and uterine dehiscence at delivery. CONCLUSIONS: Prenatal surgery for myelomeningocele reduced the need for shunting and improved motor outcomes at 30 months but was associated with maternal and fetal risks. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT00060606.).

Intrauterine repair of spina bifida: preoperative predictors of shunt-dependent hydrocephalus.

OBJECTIVE: The objective of this study was to determine which factors that are present at the time of intrauterine repair of spina bifida could predict the need for ventriculoperitoneal shunt for hydrocephalus during the first year of life. STUDY DESIGN: One hundred seventy-eight fetuses have undergone intrauterine repair of spina bifida at Vanderbilt University Medical Center since 1997. Among these, 116 fetuses had a postnatal follow-up period of at least 12 months. The primary outcome of the study was the need for a ventriculoperitoneal shunt for hydrocephalus during the first year of life. The following variables were analyzed: maternal demographics (age, race, gravidity, and parity), gestational age at the time of surgery, ventricular size, degree of hindbrain herniation (determined by magnetic resonance imaging in 33 cases), type of defect (myelomeningocele vs myeloschisis), upper level of the lesion, presence of talipes, and intraoperative use of a lumbar drain. Statistical analysis was performed with logistic regression (to test the association of fetal and maternal factors and the need for ventriculoperitoneal shunting), 2-sample t-tests for comparison of means, and receiver operating curves with the use of the probabilities that were generated by the logistic regression for both continuous and categoric versions of the factors. RESULTS: Sixty-one of 116 of the fetuses (54%) who underwent operation in utero required the placement of a ventriculoperitoneal shunt before the age of 1 year. The upper level of the lesion was the strongest predictor of shunt requirement (adjusted odds ratio per 1 level increase with the use of continuous variables [S1 through T10], 1.73 [95% CI, 1.22- 2.44]; adjusted odds ratio with the use of upper lesion level >or=L3 vs 25 weeks as a categorized variable, 3.3 [95% CI, 1.28-8.24]), and preoperative ventricular size (adjusted odds ratio per 1 unit increase with the use of continuous variables, 1.17 [95% CI, 1.01-1.36]; adjusted odds ratio with the use of ventricular size >or=14 mm vs <14 mm as a categorized variable, 3.5 [95% CI, 1.08-11.16]). Receiver operating curves with the use of the probabilities that were generated by the logistic regression analyses for both the continuous and categoric versions of the factors were compared. The area under the curve was approximately 0.81 for both methods. Thirty-eight of 48 of the fetuses (79%) with an upper level of the lesion >or=L3 required placement of a ventriculoperitoneal shunt, although 25 of 68 of the fetuses (37%) with lesions or=14 mm (27/32 fetuses) needed a shunt compared with 41% of the fetuses (34/81 fetuses) with smaller ventricles (P=.03). Seventy-one percent of the fetuses who underwent operation at >25 weeks of gestation also required shunt placement (37/52 fetuses); 39% of the fetuses (24/61 fetuses) who were treated